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Title: TU-H-CAMPUS-TeP2-04: Measurement of Stereotactic Output Factors with DNA Double-Strand Breaks

Abstract

Purpose: Radiotherapy treatment is specified by radiation dose prescriptions, but biological DNA damage actually controls treatment effectiveness. It is impractical to directly measure dose in the clinic, so we measure quantities, such as collected charge, and calculate the relationship to dose. At small fields, such as those in stereotactic radiosurgery (SRS), charged-particle equilibrium (CPE) breaks down and the accuracy of the measurement for delivered dose decreases. By measuring DNA double-strand breaks (DSB) directly, we believe treatment accuracy could improve by providing a more meaningful measurement. Methods: A DNA dosimeter, consisting of magnetic streptavidin beads attached to 4 kilobase pair DNA strands labeled with biotin and fluorescein amidite (FAM) on opposing ends, was suspended in phosphate-buffered saline (PBS). Twenty µL samples were placed in plastic micro-capillary tubes inside a water tank setup and irradiated with 10 cm, 3 cm, 1.25 cm, 0.75 cm, and 0.5 cm radiation field sizes, where the three smallest sizes were cones. After irradiation, the dosimeters were mechanically separated into beads (intact DNA) and supernatant (broken DNA/FAM) using a magnet. The fluorescence was read and the probability of DSB was calculated. This was used to calculate the output factor for an SRS beam and compared to thatmore » measured using a diode detector. Results: The output factors relative to a 10 cm field were 0.89±0.07, 0.76±0.08, 0.59±0.04, and 0.78±0.12 for the field sizes of 3 cm, 1.25 cm, 0.75 cm, and 0.5 cm, respectively. Some of the diode measurements do not fall within these uncertainties. Conclusion: This was the first attempt to measure output factors in a water tank with the DNA dosimeter. Although differences compared to the diode were observed, the uncertainty analysis ignored systematic errors. For future work, we will repeat this experiment to quantify and correct systematic errors, such as those caused by positional alignment and sample contamination. This work was funded in part by CPRIT (RP140105).« less

Authors:
; ; ; ; ; ; ; ; ; ; ;  [1]
  1. University of Texas HSC SA, San Antonio, TX (United States)
Publication Date:
OSTI Identifier:
22654068
Resource Type:
Journal Article
Resource Relation:
Journal Name: Medical Physics; Journal Volume: 43; Journal Issue: 6; Other Information: (c) 2016 American Association of Physicists in Medicine; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CHARGED PARTICLES; DOSEMETERS; LEAD SULFIDES; RADIATION DOSES; STRAND BREAKS

Citation Formats

Cline, K, Obeidat, M, Stathakis, S, Kabat, C, Markovic, M, Papanikolaou, N, Rasmussen, K, Gutierrez, A, Ha, C, Lee, S, Shim, E, and Kirby, N. TU-H-CAMPUS-TeP2-04: Measurement of Stereotactic Output Factors with DNA Double-Strand Breaks. United States: N. p., 2016. Web. doi:10.1118/1.4957692.
Cline, K, Obeidat, M, Stathakis, S, Kabat, C, Markovic, M, Papanikolaou, N, Rasmussen, K, Gutierrez, A, Ha, C, Lee, S, Shim, E, & Kirby, N. TU-H-CAMPUS-TeP2-04: Measurement of Stereotactic Output Factors with DNA Double-Strand Breaks. United States. doi:10.1118/1.4957692.
Cline, K, Obeidat, M, Stathakis, S, Kabat, C, Markovic, M, Papanikolaou, N, Rasmussen, K, Gutierrez, A, Ha, C, Lee, S, Shim, E, and Kirby, N. 2016. "TU-H-CAMPUS-TeP2-04: Measurement of Stereotactic Output Factors with DNA Double-Strand Breaks". United States. doi:10.1118/1.4957692.
@article{osti_22654068,
title = {TU-H-CAMPUS-TeP2-04: Measurement of Stereotactic Output Factors with DNA Double-Strand Breaks},
author = {Cline, K and Obeidat, M and Stathakis, S and Kabat, C and Markovic, M and Papanikolaou, N and Rasmussen, K and Gutierrez, A and Ha, C and Lee, S and Shim, E and Kirby, N},
abstractNote = {Purpose: Radiotherapy treatment is specified by radiation dose prescriptions, but biological DNA damage actually controls treatment effectiveness. It is impractical to directly measure dose in the clinic, so we measure quantities, such as collected charge, and calculate the relationship to dose. At small fields, such as those in stereotactic radiosurgery (SRS), charged-particle equilibrium (CPE) breaks down and the accuracy of the measurement for delivered dose decreases. By measuring DNA double-strand breaks (DSB) directly, we believe treatment accuracy could improve by providing a more meaningful measurement. Methods: A DNA dosimeter, consisting of magnetic streptavidin beads attached to 4 kilobase pair DNA strands labeled with biotin and fluorescein amidite (FAM) on opposing ends, was suspended in phosphate-buffered saline (PBS). Twenty µL samples were placed in plastic micro-capillary tubes inside a water tank setup and irradiated with 10 cm, 3 cm, 1.25 cm, 0.75 cm, and 0.5 cm radiation field sizes, where the three smallest sizes were cones. After irradiation, the dosimeters were mechanically separated into beads (intact DNA) and supernatant (broken DNA/FAM) using a magnet. The fluorescence was read and the probability of DSB was calculated. This was used to calculate the output factor for an SRS beam and compared to that measured using a diode detector. Results: The output factors relative to a 10 cm field were 0.89±0.07, 0.76±0.08, 0.59±0.04, and 0.78±0.12 for the field sizes of 3 cm, 1.25 cm, 0.75 cm, and 0.5 cm, respectively. Some of the diode measurements do not fall within these uncertainties. Conclusion: This was the first attempt to measure output factors in a water tank with the DNA dosimeter. Although differences compared to the diode were observed, the uncertainty analysis ignored systematic errors. For future work, we will repeat this experiment to quantify and correct systematic errors, such as those caused by positional alignment and sample contamination. This work was funded in part by CPRIT (RP140105).},
doi = {10.1118/1.4957692},
journal = {Medical Physics},
number = 6,
volume = 43,
place = {United States},
year = 2016,
month = 6
}
  • Purpose: Radiosurgery of multiple (n>4) brain metastasis lesions requires 3–4 noncoplanar VMAT arcs with excessively high monitor units and long delivery time. We investigated whether an improved optimization technique would decrease the needed arc numbers and increase the delivery efficiency, while improving or maintaining the plan quality. Methods: The proposed 4pi arc space optimization algorithm consists of two steps: automatic couch angle selection followed by aperture generation for each arc with optimized control points distribution. We use a greedy algorithm to select the couch angles. Starting from a single coplanar arc plan we search through the candidate noncoplanar arcs tomore » pick a single noncoplanar arc that will bring the best plan quality when added into the existing treatment plan. Each time, only one additional noncoplanar arc is considered making the calculation time tractable. This process repeats itself until desired number of arc is reached. The technique is first evaluated in coplanar arc delivery scheme with testing cases and then applied to noncoplanar treatments of a case with 12 brain metastasis lesions. Results: Clinically acceptable plans are created within minutes. For the coplanar testing cases the algorithm yields singlearc plans with better dose distributions than that of two-arc VMAT, simultaneously with a 12–17% reduction in the delivery time and a 14–21% reduction in MUs. For the treatment of 12 brain mets while Paddick conformity indexes of the two plans were comparable the SCG-optimization with 2 arcs (1 noncoplanar and 1 coplanar) significantly improved the conventional VMAT with 3 arcs (2 noncoplanar and 1 coplanar). Specifically V16 V10 and V5 of the brain were reduced by 11%, 11% and 12% respectively. The beam delivery time was shortened by approximately 30%. Conclusion: The proposed 4pi arc space optimization technique promises to significantly reduce the brain toxicity while greatly improving the treatment efficiency.« less
  • Ionizing radiation causes the formation of strand breaks in cellular DNA, as well as other types of lesions in the chromatin of cells. Some of the earliest investigations of the molecular basis of radiation-induced damage and the implications of enzymatic repair were done by Dr. H. S. Kaplan. Because it is difficult to assay for DNA lesions in the large mammalian genome, the authors have developed a method of assaying for DNA double-strand breaks in the supercoiled nucleosome-complexed Simian virus 40 (SV40) genome, irradiated intracellularly. In this communication they present their measurements of the DNA double-strand breaks (DSBs) to single-strandmore » breaks (SSBs) ratio obtained from the intracellularly irradiated SV40 genome. After cobalt gamma ray and X ray irradiations, this ratio is about 1/10. Their methods and results are compared with pertinent data in the literature. If the DSBs/SSBs ratio of 1/10 for cellular chromatin is correct, a substantial number of DNA double-strand breaks are formed in a mammalian cell after moderate doses (1 Gy) of radiation. The implications of different types of DNA double-strand breaks are discussed.« less
  • A number of investigations have suggested that the widely observed oxygen enhancement of radiation-induced cell killing or intracellular DNA damage requires the presence of glutathione (GSH) or other thiols. We have adapted an in vitro model system to investigate the effects of GSH on radiation-induced DNA double-strand breaks (DSBs), lesions felt to be critical to cell death. Superhelical SV40 DNA, 25 {mu}g/ml, was irradiated in air or nitrogen in the presence of 0-20 mM GSH and single-strand breaks (SSBs) and DSBs were measured using neutral gel electrophoresis/ethidium bromide fluorescence. Control experiments demonstrated that a substantial concentration of free SH wasmore » still present after irradiation. Dose-response curves for SSBs and DSBs in air or nitrogen were predominantly linear at all GSH concentrations tested from 0-20 mM, except for 20 mM GSH in nitrogen, indicating that both SSBs and DSBs in nitrogen at 20 mM GSH, suggesting additional damage, rather than the expected additional protection. The possible mechanism for a damaging effect from GSH is discussed. Oxygen enhancement ratios (OERs) were calculated from the slopes of dose-response curves. The OERs for SSBs did not differ substantially from those for DSBs at the same [GSH], contrary to the observations of Prise. The OERs for SSBs and DSBs peaked at 6.5 and 8, respectively, at 5 mM GSH. These similarities suggest that the much lower OERs (2.5-3.0) generally reported for radiation killing of cells, which also typically contain about 5 mM GSH, cannot be accounted for by differences in OER between lethal lesions, represented by DSBs, and nonlethal lesions, represented by SSBs. In view of the present results, another possible explanation, that intracellular compounds other than reduced thiols are important in the chemical modification of the response of DNA to radiation, seems to be much more likely. 41 refs., 5 figs.« less
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